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Updated: Mar 18, 2026
Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy
Published on: August 19, 2021
Uses and abuses of macropinocytosis
Gareth Bloomfield1, Robert R Kay2
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK garethb@mrc-lmb.cam.ac.uk.
Abstract:
Macropinocytosis is a means by which eukaryotic cells ingest extracellular liquid and dissolved molecules. It is widely conserved amongst cells that can take on amoeboid form and, therefore, appears to be an ancient feature that can be traced back to an early stage of evolution. Recent advances have highlighted how this endocytic process can be subverted during pathology - certain cancer cells use macropinocytosis to feed on extracellular protein, and many viruses and bacteria use it to enter host cells. Prion and prion-like proteins can also spread and propagate from cell to cell through macropinocytosis. Progress is being made towards using macropinocytosis therapeutically, either to deliver drugs to or cause cell death by inducing catastrophically rapid fluid uptake. Mechanistically, the Ras signalling pathway plays a prominent and conserved activating role in amoebae and in mammals; mutant amoebae with abnormally high Ras activity resemble tumour cells in their increased capacity for growth using nutrients ingested through macropinocytosis. This Commentary takes a functional and evolutionary perspective to highlight progress in understanding and use of macropinocytosis, which is an ancient feeding process used by single-celled phagotrophs that has now been put to varied uses by metazoan cells and is abused in disease states, including infection and cancer.
Insights
Macropinocytosis, an ancient cellular feeding process, is crucial for nutrient uptake and cell entry. This conserved mechanism is exploited in diseases like cancer and infection, but also offers therapeutic potential.
Area of Science:
- Cell Biology
- Evolutionary Biology
- Pathology
Background:
- Macropinocytosis is a conserved endocytic process enabling eukaryotic cells to ingest extracellular fluid and molecules.
- This ancient feeding mechanism is vital for single-celled organisms and has been adopted by metazoan cells.
- Recent research reveals its significant roles in pathology, including cancer and host-pathogen interactions.
Purpose of the Study:
- To provide a functional and evolutionary perspective on macropinocytosis.
- To highlight recent advances in understanding its mechanisms and therapeutic applications.
- To underscore its dual role in normal cellular function and disease states.
Main Methods:
- Review of current literature on macropinocytosis.
- Analysis of evolutionary conservation across species.
- Examination of mechanistic insights, particularly the Ras signaling pathway.
Main Results:
- Macropinocytosis is an ancient, conserved process fundamental to cellular life.
- Pathogenic agents and cancer cells hijack macropinocytosis for invasion and nutrient acquisition.
- The Ras signaling pathway is a key conserved activator of macropinocytosis.
- Therapeutic strategies targeting macropinocytosis are under development for drug delivery and cancer treatment.
Conclusions:
- Macropinocytosis is a versatile cellular process with deep evolutionary roots.
- Its subversion in disease presents challenges but also therapeutic opportunities.
- Further research into macropinocytosis mechanisms can unlock novel treatment strategies.
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